The Johns Hopkins Drug Abuse Research Center focuses on the Dynamics of Signaling by Molecular Messengers Relevant to Actions of Drugs of Abuse, an approach, which, over the years, has led to major insights into how novel proteins and small molecular messengers provide the neuronal signaling which underlies actions of psychotropic drugs. The ongoing and proposed projects of the four principal investigators interdigitate and are notably synergistic. Snyder addresses novel molecular messengers underlying drug actions including (1) NO/GAPDH nuclear signaling (2) Inositol hexakisphosphate kinase-2 (IP6K2) impacting cell death and neurotoxicity and (3) Actions of inositol polyphosphate multikinase (IPMK) that impact brain function. Worley deals with Rheb1 and mTOR signaling with a focus on (1) Translational mechanisms and transcriptional events regulated by mTOR, (2) The role of Rheb1 in myelination in the brain and (3) LanCL1 impacting signaling and growth factor dependent neuronal survival. The Dawsons address dynamics of poly (ADP-ribose) and how it regulates maladaptive stress responses that occur with psychotropic drug action. Specific areas of interest include (1) Iduna, a major novel protein regulating poly(ADP-ribose) disposition and cell survival, (2) Iduna influences upon epigenetic modifications (3) Influences of Iduna upon microRNA processing. Baraban deals with how the translin/trax RNAse complex regulates microRNA processing and responses to cocaine with a focus upon (1) Identifying physiologic targets of translin/trax, (2) Determining how deletion of translin interfaces with signaling pathways that are regulated by cocaine, and (3) Elucidating how striatal translin affects behavioral responses to cocaine.